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Intensified Conditioning Regimen With High-Dose-Etoposide for Allo-HSCT for Adult Acute Lymphoblastic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier:
NCT01457040
First received: October 11, 2011
Last updated: October 29, 2013
Last verified: October 2013

October 11, 2011
October 29, 2013
October 2011
October 2013   (final data collection date for primary outcome measure)
Over Survival [ Time Frame: 3 years after HSCT ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01457040 on ClinicalTrials.gov Archive Site
Relapse-Free-Survival [ Time Frame: 3 years after HSCT ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Intensified Conditioning Regimen With High-Dose-Etoposide for Allo-HSCT for Adult Acute Lymphoblastic Leukemia
A Prospective Study of Intensified Conditioning Regimen With High-Dose-Etoposide for Allogeneic Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia in China

Evolving paradigms in the treatment of adult ALL include the application of intense pediatric regimens to the treatment of adolescents and young adults (AYA) and the optimization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the cure of patients. The Cancer and Leukemia Group B (CALGB) and the Children's Cancer Group (CCG) first asked whether AYA between the ages of 16 and 20 fared differently whether they were treated on pediatric protocols. The results of this study demonstrated that although the complete remission rates were identical for the AYAs treated on the CALGB and CCG trials, the AYAs had a 63% event-free survival (EFS) and 67% OS at 7 years on the CCG trials compared with 34% and 46%, respectively, on the CALGB trials.

High relapse and transplantation-related-mortality still remains great challenge for HSCT of adult ALL, which both range between 25% and 30%. Recently, risk-adapted indication and optimization of conditioning regimen are highlighted, which aiming to reduce TRM and relapse rate, respectively.City of Hope National Medical Center studied the substitution of etoposide (VP-16) for CY in the treatment of ALL patients receiving HCT. The result suggested that etoposide and TBI are associated with a decreased relapse rate following transplantation for ALL, compared with those receiving CY and TBI. Japanese and Germany reports pronounced the advantage of VP-16 in intensified regimen for adult ALL. On the same time, the investigators previous researches have confirmed the effect and safety of FA-intensified conditioning regimen on relapse and refractary leukemia.

Based on mentioned above, the investigators speculate that VP-16-intensified conditioning regimen could improve the outcome for adult ALL. The potential mechanism will be attributed to reduce MRD and promote GVL effect via providing enough time-window for immuno-reconstitution by high-dose preparative regimen.

In the first decade of the new millennium, multiple studies have begun to change our thinking about the treatment of adults with acute lymphoblastic leukemia (ALL). In pediatric patients cure rates in the range of 80% to 90% are now attainable. While adult patients with ALL now have a 90% complete remission (CR) with modern chemotherapy, most patients will relapse, and leukemia-free survival with 3 to 7 years of follow-up in large series is only in the range of 30% to 40%. The poor outcome of chemotherapy in adults with ALL as compared to children relates to multiple factors, including poor tolerance of intensive courses of chemotherapy and a higher incidence of poor prognostic subtypes of ALL such as Philadelphia chromosome-positive ALL and a lower incidence of favorable subtypes such as the t (12; 21).

Evolving paradigms in the treatment of adult ALL include the application of intense pediatric regimens to the treatment of adolescents and young adults (AYA) and the optimization of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the cure of patients. Adult regimens are typically less intense than pediatric regimens. The Cancer and Leukemia Group B (CALGB) and the Children's Cancer Group (CCG) first asked whether AYA between the ages of 16 and 20 fared differently whether they were treated on pediatric protocols. The results of this study demonstrated that although the complete remission rates were identical for the AYAs treated on the CALGB and CCG trials, the AYAs had a 63% event-free survival (EFS) and 67% OS at 7 years on the CCG trials compared with 34% and 46%, respectively, on the CALGB trials. These results have prompted new studies where pediatric ALL regimens have been adapted to the treatment of younger adults. With short follow-up, GRAALL-2003 reports suggest EFS and OS outcomes in the range of 60%. This improved outcome was more pronounced in the standard-risk patients with a donor who had an OS at 5 years of 69%. On the same time, our previous researches have confirmed the effect and safety of FA-intensified conditioning regimen on relapse and refractary leukemia.

Based on mentioned above, we speculate that VP-16-intensified conditioning regimen could improve the outcome for adult ALL. The potential mechanism will be attributed to reduce MRD and promote GVL effect via providing enough time-window for immuno-reconstitution by high-dose preparative regimen.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Lymphoblastic Leukemia
  • Stem Cell Transplantation, Hematopoietic
  • Other: TBI/CY/VP-16
    CR1 Cohort will receive condition regimen of TBI/CY/VP-16: TBI: 4.5Gy/d, -5d, -4d; CY: 60mg/kg/d, -3d, -2d; VP-16: 15mg/kg/d, -3d, -2d
  • Other: FA-TBI/CY/VP-16
    Non-CR1 Cohort will receive conditioning regimen of FA-TBI/CY/VP-16: Flu: 35mg/m2/d: -10->-6d; AraC: 1g/m2/d, -10d->-6d; TBI: 4.5Gy/d, -5d,-4d; CY:60mg/kg/d, -3d, -2d; VP-16: 15mg/kg, -3d, -2d
  • Experimental: First Complete Remission of ALL
    CR1 Cohort: subject with ALL in First Complete Remission (CR)
    Intervention: Other: TBI/CY/VP-16
  • Experimental: Non-First Complete Remission
    Non-CR1 Cohort: subject with ALL beyond first CR, or not remission
    Intervention: Other: FA-TBI/CY/VP-16

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
100
Not Provided
October 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age: 16 years to 65 years
  2. Diagnosis of acute lymphoblastic leukemia
  3. Disease condition in CR1 or Non-CR1
  4. Patient received allogeneic hematopoietic stem cell transplantation
  5. The informed consent form has been signed.
  6. The following exclusion criteria are excluded.

Exclusion Criteria:

  1. Patient with severe cardiac dysfunction with less than 50% EF
  2. Patient with severe lung dysfunction
  3. Patient with severe hepatic or renal dysfunction with more than 3 times the upper limit of normal range (ULN) of serum ALT or AST levels, or with more than 2 times the upper limit of normal range (ULN) of serum TBIL level or less than 40% of normal prothrombin time activity (PTA); or with more than 2 times the ULN of serum Cr
  4. Patient with severe active infection
  5. Patient with allergy history about suspected drug in conditioning regimen
  6. Patient with other conditions considered unsuitable for the study
Both
16 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
China
 
NCT01457040
HDE-ALL-2011
Yes
Nanfang Hospital of Southern Medical University
Nanfang Hospital of Southern Medical University
Not Provided
Principal Investigator: Qifa Liu, MD Department of Hematology, Nanfang Hospital
Nanfang Hospital of Southern Medical University
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP